The sensory nerves of the anterior uvea, or the ciliary body and the iris are critically involved in the mediation of afferent input, as well as inflammatory reactions related to the axon reflex. Recent evidence suggests that some of these fibers may be peptidergic rather than adrenergic or cholinergic, and their possible role in vegetative and motor functions of the anterior segment has been suggested. These anatomical observations are particularly important since the ocular response to nociceptive stimuli usually involves a long-lasting, noncholinergic miosis, hypermia, breakdown of the blood-aqueous barrier, and elevation of intraocular pressure (IOP). In spite of the extensive research, the exact mechanism of the irritative response or the different transmitters involved have remained elusive. In this application, four peptides have been selected for study. Alpha-MSH is a circulating pituitary hormone, NT and SP may be considered members of a family of peptides present in the CNS and peripheral sensory fibers, and TRH has been shown to antagonize many of the CNS effects of NT. We propose, in general, first to define the immunohistochemical distribution of these peptides in structures of the anterior segment involved in IOP and pupillary control. Second, to determine the role of these peptides in anterior segment physiology, a variety of techniques will be brought to bear on the problem--peptidase inhibitors, sensory denervation, specific antibodies to peptides, studies of cyclic nucleotides, and radioimmunoassay procedures. This research holds promise for uncovering new and important regulatory components involved in motor and vegetative functions of the anterior segment. Expanding our understanding of pupillary control beyond the classical autonomic mechanisms will provide additional knowledge of ocular physiology with relevant clinical ramifications. Further understanding of the nature of the blood-acqueous-barrier may contribute to explain the relative efficacy of the current drug therapy employed in the management of certain ocular disorders, including uveitis, ocular hypertension, and glaucoma.